Eculizumab in neonatal hemolytic uremic syndrome with homozygous factor H deficiency
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Neonatal atypical hemolytic uremic syndrome (aHUS) is a rare but severe disease that is mainly due to methylmalonic aciduria or genetic complement abnormalities. Traditional management of aHUS includes plasma infusion/exchange, but in small or unstable infants, plasma exchange can be challenging because of high extracorporeal volume and difficulty to obtain an adequate venous access. The C5 complement blocker eculizumab has become a cornerstone of first-line management of aHUS due to complement deregulation in older patients. However, little data are available on its use in neonatal aHUS.
We report on an 11-day-old neonate with severe aHUS (myocardial impairment, respiratory failure, acute kidney disease requiring hemodiafiltration) due to homozygous factor-H deficiency. She received early treatment with eculizumab as first-line therapy and completely recovered within 5 days. A second dose of eculizumab was administered 7 days after the first infusion, followed by a dose every 2 weeks for 2 months and then every 3 weeks, at the same dosage (300 mg). With more than 24 months of follow-up, renal function remains normal.
We report on the long-term efficacy and safety of eculizumab as first-line therapy in neonatal aHUS. However its use still requires optimization in terms of indications and administration (frequency, dosage).
KeywordsAtypical hemolytic uremic syndrome Homozygous Factor H deficiency Eculizumab Infant
The authors would like to thank Thabo Mahendiran, Dr Agnès Veyradier (unité INSERM, Hôpital Kremlin-Bicêtre, Paris) and Pr Chantal Loirat (Hôpital Robert Debré, Paris) for their help.
Financial disclosure statement
Conflicts of interest
Veronique Fremeaux-Bacchi had received fees from Alexion Pharmaceuticals for invited lectures and participation on advisory boards
- 1.Ariceta G, Besbas N, Johnson S, Karpman D, Landau D, Licht C, Loirat C, Pecoraro C, Taylor CM, Van de Kar N, Vandewalle J, Zimmerhackl LB, European Paediatric Study Group for HUS (2008) Guideline for the investigation and initial therapy of diarrhea-negative hemolytic uremic syndrome. Pediatr Nephrol 24:687–696PubMedCrossRefGoogle Scholar
- 2.Sellier-Leclerc A-L, Fremeaux-Bacchi V, Dragon-Durey M-A, Macher M-A, Niaudet P, Guest G, Boudailliez B, Bouissou F, Deschenes G, Gie S, Tsimaratos M, Fischbach M, Morin D, Nivet H, Alberti C, Loirat C, French Society of Pediatric Nephrology (2007) Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome. J Am Soc Nephrol 18:2392–2400PubMedCrossRefGoogle Scholar
- 14.Habibi I, Sfar I, Ben Alaya W, Methlouthi J, Ayadi A, Brahim M, Blouin J, Dhagbouj R, Ben Rhomdhane T, Makhlouf M, Aouadi H, Ayed-Jendoubi S, Fremeaux-Bacchi V, Sfar T, Ben Abdallah T, Ayed K, Gorgi Y (2010) Atypical hemolytic uremic syndrome and mutation analysis of factor H gene in two Tunisian families. Int J Nephrol Renovasc Dis 3:85–92PubMedPubMedCentralGoogle Scholar
- 16.Legendre CM, Licht C, Muus P, Greenbaum LA, Babu S, Bedrosian C, Bingham C, Cohen DJ, Delmas Y, Douglas K, Eitner F, Feldkamp T, Fouque D, Furman RR, Gaber O, Herthelius M, Hourmant M, Karpman D, Lebranchu Y, Mariat C, Menne J, Moulin B, Nürnberger J, Ogawa M, Remuzzi G, Richard T, Sberro-Soussan R, Severino B, Sheerin NS, Trivelli A, Zimmerhackl LB, Goodship T, Loirat C (2013) Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med 368:2168–2169CrossRefGoogle Scholar